Furthermore the complete blockade of the responses induced by BK by its antagonist HOE-140 showed that only B2R activation was responsible for the enhanced responses induced by

BK in overexpressing endothelial aorta isolated from TGR(Tie2B1). It was also found that HOE-140 had no effect on DBK-induced relaxation, confirming what was reported by [17] that the increased response induced by DBK in TGR(Tie2B1) was inhibited specifically by the antagonist of B1R. These authors reported that the responses to DBK were completely blocked by L-NAME in the isolated aorta from TGR(Tie2B1) rats which is in agreement with our study wherein a complete inhibition of BK induced effect by L-NAME was found, indicating that relaxant responses Selleck Panobinostat induced by the kinins in the rat aorta are highly dependent on NO generation. It was reported that mice overexpressing B1R in multiple tissues induced hypertensive response to B1R agonist, exacerbated paw and edema induced by carrageenan and high susceptibility to endotoxic shock induced by lipopolysaccharide [19]. The present study showed that B2R was surprisingly overexpressed in the endothelium of thoracic aorta from TGR(Tie2B1) rat. This finding was unexpected since a downregulation should occur as a counter regulatory mechanism for overexpression of B1R. It has been reported that the lack of one kinin receptor

is compensated Romidepsin concentration by the up-regulation of the other subtype, as shown in the case of deletion of B2R [10], [12] and [36] and of

B1R [16] and [28]. In another study [28], lipopolysaccharide treatment caused enhanced B2R mRNA which was further increased in B1KO mice with increased mortality. Although some studies have been reported about overexpression of B1R [17] and [19] or B2R [33] assessing the importance of the overexpressed receptor, the expression of the other remaining receptor subtype has not been determined. The enhanced B2R mRNA expression in TGR(Tie2B1) rat was correlated with the increased responsiveness of rat aorta to its agonist BK. The finding that the ability of ACE to convert GPX6 AngI to AngII was not reduced neither the ACE mRNA was altered, provided evidence that the increase in the BK reactivity was not modulated by ACE activity due to the high expression of the B2R. This conclusion could not confirm an effect of ACE/kinin B2R interaction modulating ACE activity as previously described [20] and [27]. It is noteworthy that was found no evidence for increased activation of AT1R since the vascular reactivity to AngII was maintained in the aorta isolated from (TGR(Tie2B1)) rats. Therefore the hypothesis that a spontaneous heterodimerization of AngII and BK receptors could trigger the AT1R activation was not confirmed in contrast to that previously reported [1]. In conclusion, transgenic rats overexpressing kinin B1R exclusively in the endothelium of TGR(Tie2B1) rats were shown to overexpress the kinin B2R and to cause increased responsiveness to BK.